Comparison of early onset sepsis and community-acquired late onset sepsis in infants less than 3 months of age

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Abstract

Background

We compared demographic and clinical characteristics of early-onset sepsis (EOS) and community-acquired late onset sepsis (CA-LOS) in infants.

Methods

Our medical center is the sole hospital in southern-Israel, enabling incidence calculations. EOS (<7 days) and CA-LOS (7–90 days) episodes recorded between 2007 and 2013 were reviewed. Univariate and multivariate analyses were performed.

Results

70 EOS and 114 CA-LOS episodes were recorded. The respective mean ± SD annual rates per 1,000 live-births were 0.66 ± 0.16 and 1.03 ± 0.23. Prematurity (42.9 % vs. 17.0 %), premature rupture of membranes (PROM; 22.9 % vs. 1.9 %), leukopenia (29.0 % vs. 11.6 %), thrombocytopenia (44.9 % vs. 14.3 %) and Streptococcus agalactiae infections (22.7 % vs. 8.1 %) were more common in EOS. Fever (25.4 % vs. 79.1 %) and Streptococcus pneumoniae infections (1.3 % vs. 12.9 %) were less common in EOS. In both groups, Gram-negative bacteria predominated (~60 %). Longer hospitalization duration (23.3 ± 25.1 vs. 10.3 ± 8.6 days) and higher case fatality rate (20.0 % vs. 5.3 %) were noted in EOS. Antibiotic resistance rates to empiric EOS and CA-LOS treatments were 0.0 % and 1.2 %, respectively.

In multivariate analysis, adjusting for prematurity and ethnicity, PROM, central line, low Apgar-score, low birth-weight, ventilation support and non-vaginal delivery were risk factors for EOS. Normal temperature, thrombocytopenia and leukopenia characterized EOS.

Conclusion

EOS and CA-LOS rates were low in Jewish compared with Bedouin infants. EOS was characterized by higher rates of perinatal risk factors, S. agalactiae infections, normal temperature, thrombocytopenia, leukopenia and mortality, while fever and S. pneumoniae infections were common in CA-LOS. Current initial antibiotic regimens seem adequate, considering the susceptibility patterns of the isolated pathogens

Electronic supplementary material

The online version of this article (doi:10.1186/s12887-016-0618-6) contains supplementary material, which is available to authorized users.

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Most cited references 33

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An overview of global GBS epidemiology.

T Heath, Kirsty Le Doare (2013)

Streptococcus agalactiae (group B streptococcus (GBS)), remains the leading cause of neonatal sepsis and meningitis in many countries and an important cause of disease in pregnant women, immunocompromised adults and the elderly. Intrapartum antibiotic strategies have reduced the incidence of early-onset neonatal GBS where applied, but have had no impact on late onset GBS infection and only a limited impact on disease in pregnant women. In low/middle income settings, the disease burden remains uncertain although in several countries of Southern Africa appears comparable to that of high-income countries. Disease may be rapidly fulminating and cases therefore missed before appropriate samples are obtained. This may lead to significant underestimation of the true burden and be a particular issue in many African and Asian countries; comprehensive epidemiological data from such countries are urgently required. The available data suggest that the serotype distribution of GBS isolates is similar in Africa, Western Pacific, Europe, the Americas and the Eastern Mediterranean regions and has not changed over the past 30 years. Five serotypes (Ia, Ib, II, III, V) account for the majority of disease; conjugate vaccines including some or all of these serotypes therefore hold great promise for preventing this important disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

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Serial serum C-reactive protein levels in the diagnosis of neonatal infection.

W E Benitz, M. Han, A. Madan … (1998)

To evaluate serial serum C-reactive protein (CRP) levels for diagnosis of neonatal infection. A regional intensive care nursery and two community intensive care nurseries. All neonates treated for suspected bacterial infection were prospectively evaluated using a standardized clinical pathway. Infants were categorized as having proven sepsis (bacteria isolated from blood, cerebrospinal fluid, or urine culture), probable sepsis (clinical and laboratory findings consistent with bacterial infection without a positive culture), or no sepsis (findings not consistent with sepsis), without consideration of CRP levels. Infants whose blood cultures yielded skin flora but who demonstrated no other signs of bacterial infection were not considered to have sepsis. CRP levels were determined at the initial evaluation and on each of the next two mornings. Sensitivity, specificity, predictive values, and likelihood ratios were calculated for the first (CRP #1), second (CRP #2), higher of the second and third (CRP #2 and #3), or highest of all three CRP levels (CRP x 3). Sepsis was suspected within the first 3 days after birth in 1002 infants (early-onset) and on 184 occasions in 134 older infants (late-onset). There were 20 early-onset and 53 late-onset episodes of proven sepsis, and 74 early-onset and 12 late-onset episodes of probable sepsis. CRP #1 had sensitivities of 39.4% and 64.6% for proven or probable sepsis and 35.0% and 61.5% for proven sepsis in early-onset and late-onset episodes, respectively. CRP levels on the morning after the initial evaluation (CRP #2) had higher sensitivities (92. 9% and 85.0% for proven or probable sepsis and 78.9% and 84.4% for proven sepsis in early-onset and late-onset episodes, respectively), and normal results were associated with lower likelihoods of infection (likelihood ratios for normal results of 0.10 and 0.19 for proven or probable sepsis and 0.27 and 0.21 for proven sepsis, in early-onset and late-onset episodes, respectively). Three serial serum CRP levels had sensitivities of 97.8% and 98.1% for proven or probable sepsis and 88.9% and 97.5% for proven sepsis in early-onset and late-onset episodes, respectively. The negative predictive values for CRP x 3 were 99.7% and 98.7% for both proven or probable sepsis and for proven sepsis in early-onset and late-onset episodes, respectively. A CRP level obtained at the time of the initial evaluation can be omitted without significant loss of sensitivity or negative predictive value: the sensitivities of CRP #2 and #3 were 97.6% and 94.4% for proven or probable sepsis and 88.9% and 96.4% for proven sepsis in early-onset and late-onset episodes, respectively; negative predictive values were 99.7% both for proven and for proven or probable early-onset sepsis, 97.6% for proven or probable late-onset infection, and 98.8% for proven late-onset infection. Serial normal CRP levels were associated with a markedly reduced likelihood of infection as compared with that in the entire population before testing, with likelihood ratios ranging from 0.03 to 0.16 for the various subgroups. Maximum CRP levels >3 mg/dL had positive predictive values >20% for proven or probable early-onset infections and for proven or probable and proven late-onset infections, but only those >6 mg/dL had such a high positive predictive value for proven early-onset sepsis. Serial CRP levels are useful in the diagnostic evaluation of neonates with suspected infection. Two CRP levels <1 mg/dL obtained 24 hours apart, 8 to 48 hours after presentation, indicate that bacterial infection is unlikely. The sensitivity of a normal CRP at the initial evaluation is not sufficient to justify withholding antibiotic therapy. The positive predictive value of elevated CRP levels is low, especially for culture-proven early-onset infections.

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Immaturity of infection control in preterm and term newborns is associated with impaired toll-like receptor signaling.

K Herkner, K Sadeghi, Arnold Pollak … (2007)

The impaired infection control related to the functional immaturity of the neonatal immune system is an important cause of infection in preterm newborns. We previously reported that constitutive Toll-like receptor (TLR) 4 expression and cytokine secretion on lipopolysaccharide (LPS) stimulation increases with gestational age. Here, we analyzed constitutive monocyte TLR2 expression and evaluated the expression profiles of the proximal downstream adapter molecule myeloid differentiation factor 88 (MyD88). We further investigated activation of protein kinases p38 and extracellular regulated kinsase (ERK) 1/2 in CD14 monocytes after ex vivo stimulation with bacterial TLR ligands (LPS and lipoteichoic acid [LTA]). The functional outcome of the stimulation was determined by cytokine secretion. Monocytes from 31 preterm newborns (<30 weeks of gestation, n=16; 30-37 weeks of gestation, n=15), 10 term newborns, and 12 adults were investigated. In contrast to TLR4 expression, TLR2 levels did not differ between age groups. However, MyD88 levels were significantly lower in preterm newborns. Activation of p38 and ERK1/2 was impaired in all newborn age groups after stimulation with TLR-specific ligands. Accordingly, after LTA stimulation, the levels of interleukin (IL)-1 beta , IL-6, and IL-8 cytokine production were substantially lower (P<.001) in preterm newborns than in adults. The reduced functional response to bacterial cell wall components appears to be part of the functional immaturity of the neonatal immune system and might predispose premature newborns to bacterial infection.

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Author and article information

Contributors

Shlomi Bulkowstein: sbulko@gmail.com

Shalom Ben-Shimol: +972-8 6400547 , shalomb2@clalit.org.il

Noga Givon-Lavi: givon@bgu.ac.il

Rimma Melamed: rimmam@bgu.ac.il

Eilon Shany: EilonS@clalit.org.il

David Greenberg: dudi@bgu.ac.il

Journal

Journal ID (nlm-ta): BMC Pediatr

Journal ID (iso-abbrev): BMC Pediatr

Title: BMC Pediatrics

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2431

Publication date (Electronic): 7 July 2016

Publication date PMC-release: 7 July 2016

Publication date Collection: 2016

Volume: 16

Electronic Location Identifier: 82

Affiliations

[ ]Pediatric Infectious Disease Unit, Soroka University Medical Center, P.O. Box 151, Beer-Sheva, 84101 Israel

[ ]Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel

[ ]Neonatology Unit, Soroka University Medical Center, Beer Sheva, Israel

Article

Publisher ID: 618

DOI: 10.1186/s12887-016-0618-6

PMC ID: 4936327

PubMed ID: 27387449

SO-VID: c571b3e0-16d7-41ec-b381-abd684d9fa20

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 3 September 2015

Date accepted : 30 June 2016

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ScienceOpen disciplines: Pediatrics

Keywords: neonatal sepsis,early vs. late onset,infant, infection,group b streptococcus

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ScienceOpen disciplines: Pediatrics

Keywords: neonatal sepsis, early vs. late onset, infant, infection, group b streptococcus

Comparison of early onset sepsis and community-acquired late onset sepsis in infants less than 3 months of age

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Abstract

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Conclusion

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Most cited references 33

An overview of global GBS epidemiology.

Serial serum C-reactive protein levels in the diagnosis of neonatal infection.

Immaturity of infection control in preterm and term newborns is associated with impaired toll-like receptor signaling.

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